Fexofenadine hydrochloride, the major active metabolite of
terfenadine, is an antihistamine with selective peripheral H-receptor antagonist activity. Both enantiomers of
fexofenadine hydrochloride displayed approximately equipotent antihistaminic
effects. Fexofenadine hydrochloride inhibited antigen-induced bronchospasm in
sensitized guinea pigs and histamine release from peritoneal mast cells in rats.
The clinical significance of these findings is unknown. In laboratory animals,
no anticholinergic or alpha-adrenergic blocking effects
were observed. Moreover, no sedative or other central nervous system effects
were observed. Radiolabeled tissue distribution studies in rats indicated that
fexofenadine does not cross the blood-brain barrier.

Fexofenadine Hydrochloride Tablets are indicated for the relief
of symptoms associated with seasonal allergic rhinitis in adults and children 6
years of age and older. Symptoms treated effectively were sneezing, rhinorrhea,
itchy nose/palate/throat, itchy/watery/red eyes.

Fexofenadine Hydrochloride Tablets are indicated for treatment of
uncomplicated skin manifestations of chronic idiopathic urticaria in adults and
children 6 years of age and older. It significantly reduces pruritus and the
number of wheals.

Fexofenadine Hydrochloride Tablets are contraindicated in
patients with known hypersensitivity to any of its ingredients.

Fexofenadine Hydrochloride Tablets are prescribed for the relief of symptoms
of seasonal allergic rhinitis or for the relief of symptoms of chronic
idiopathic urticaria (hives). Patients should be instructed to take Fexofenadine
Hydrochloride Tablets only as prescribed. Do not exceed the recommended dose. If
any untoward effects occur while taking Fexofenadine Hydrochloride Tablets,
discontinue use and consult the doctor.

The product should not be used by patients who are hypersensitive to it or to
any of its ingredients.

Patients should be told that this product should be used in pregnancy or
lactation only if the potential benefit justifies the potential risk to the
fetus or nursing infant.

Patients should be advised to take the tablet with water. Patients should
also be advised to store the medication in a tightly closed container in a cool,
dry place, away from children.

The changes in plasma levels were within the range of plasma levels achieved
in adequate and well-controlled clinical trials.

The mechanism of these interactions has been evaluated in in vitro, in situ, and in vivo
animal models. These studies indicate that ketoconazole or erythromycin
co-administration enhances fexofenadine gastrointestinal absorption. This
observed increase in the bioavailability of fexofenadine may be due to
transport-related effects, such as p-glycoprotein. In
vivo animal studies also suggest that in addition to enhancing
absorption, ketoconazole decreases fexofenadine gastrointestinal secretion,
while erythromycin may also decrease biliary excretion.

The carcinogenic potential and reproductive toxicity of
fexofenadine hydrochloride were assessed using terfenadine studies with adequate
fexofenadine hydrochloride exposure (based on plasma
area-under-the-concentration vs. time [AUC] values). No evidence of
carcinogenicity was observed in an 18-month study in mice and in a 24-month
study in rats at oral doses up to 150 mg/kg of terfenadine (which led to
fexofenadine exposures that were approximately 3 and 5 times the exposure from
the maximum recommended human daily oral dose of fexofenadine hydrochloride in
adults [180 mg] and children [60 mg] respectively .

In rat dietary fertility studies, dose-related reductions in implants and
increases in postimplantation losses were observed at an oral dose of 150 mg/kg
of terfenadine (which led to fexofenadine hydrochloride exposures that were
approximately 3 times the exposure of the maximum recommended human daily oral
dose of 180 mg fexofenadine hydrochloride). In mice, fexofenadine hydrochloride
produced no effect on male or female fertility at average dietary doses up to
4438 mg/kg (approximately 10 times the maximum recommended human daily oral dose
of fexofenadine hydrochloride 180 mg based on comparison of AUCs).

PREGNANCY

Category C.

There was no evidence of teratogenicity in rats or rabbits at oral doses of
terfenadine up to 300 mg/kg (which led to fexofenadine exposures that were
approximately 3 and 30 times, respectively, the exposure from the maximum
recommended human daily oral dose of fexofenadine hydrochloride of 180 mg based
on comparison of AUCs).

In mice, no adverse effects and no teratogenic effects during gestation were
observed with fexofenadine at dietary doses up to 3730 mg/kg (approximately 15
times the maximum recommended human daily oral dose of fexofenadine
hydrochloride 180 mg based on comparison of AUCs).

There are no adequate and well controlled studies in pregnant women.
Fexofenadine should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.

Dose-related decreases in pup weight gain and survival were
observed in rats exposed to an oral dose of 150 mg/kg of terfenadine
(approximately 3 times the maximum recommended human daily oral dose of
fexofenadine hydrochloride of 180 mg in adults based on comparison of
fexofenadine hydrochloride AUCs).

The recommended dose in patients 6 to 11 years of age is based on
cross-study comparison of the pharmacokinetics of fexofenadine hydrochloride in
adults and pediatric subjects and on the safety profile of fexofenadine
hydrochloride in both adult and pediatric subjects at doses equal to or higher
than the recommended doses.

The safety of fexofenadine hydrochloride tablets at a dose of 30 mg twice
daily has been demonstrated in 438 pediatric subjects 6 to 11 years of age in
two placebo-controlled 2-week seasonal allergic rhinitis trials. The safety of
fexofenadine hydrochloride for the treatment of chronic idiopathic urticaria in
subjects 6 to 11 years of age is based on cross-study comparison of the
pharmacokinetics of fexofenadine hydrochloride in adult and pediatric subjects
and on the safety profile of fexofenadine in both adult and pediatric subjects
at doses equal to or higher than the recommended dose.

The effectiveness of fexofenadine hydrochloride for the treatment of seasonal
allergic rhinitis in subjects 6 to 11 years of age was demonstrated in 1 trial
(n=411) in which fexofenadine hydrochloride tablets 30 mg twice daily
significantly reduced total symptom scores compared to placebo, along with
extrapolation of demonstrated efficacy in subjects aged 12 years and above, and
the pharmacokinetic comparisons in adults and children. The effectiveness of
fexofenadine hydrochloride for the treatment of chronic idiopathic urticaria in
patients 6 to 11 years of age is based on an extrapolation of the demonstrated
efficacy of fexofenadine hydrochloride in adults with this condition and the
likelihood that the disease course, pathophysiology and the drug's effect are
substantially similar in children to that of adult patients.

Three clinical safety studies comparing 15 mg twice daily (n=85) and 30 mg
twice daily (n=330) of an experimental formulation of fexofenadine to placebo
(n=430) have been conducted in pediatric subjects aged 6 months to 5 years. In
general, fexofenadine hydrochloride was well tolerated in these studies. No
unexpected adverse events were seen given the known safety profile of
fexofenadine and likely adverse reactions for this patient population. (See ADVERSE REACTIONS and CLINICAL
PHARMACOLOGY.)

The safety and effectiveness of fexofenadine hydrochloride in pediatric
patients under 6 years of age have not been established.

Effects on steady-state fexofenadine pharmacokinetics after 7 days of
co-administration with fexofenadine hydrochloride 120 mg every 12 hours (two
times the recommended twice daily dose) in healthy volunteers (n=24)

Concomitant Drug

CmaxSS
(Peak plasma concentration)

AUCss(0–12h)
(Extent of systemic exposure)

Erythromycin

+82%

+109%

(500 mg every 8 hrs)

Ketoconazole

+135%

+164%

(400 mg once daily)

In placebo-controlled seasonal allergic rhinitis clinical trials
in subjects 12 years of age and older, which included 2461 subjects receiving
fexofenadine hydrochloride capsules at doses of 20 mg to 240 mg twice daily,
adverse events were similar in fexofenadine hydrochloride- and placebo-treated
subjects. All adverse events that were reported by greater than 1% of subjects
who received the recommended daily dose of fexofenadine hydrochloride (60 mg
capsules twice daily), and that were more common with fexofenadine hydrochloride
than placebo, are listed in Table 1.

In a placebo-controlled clinical study in the United States, which included
570 subjects aged 12 years and older receiving fexofenadine hydrochloride
tablets at doses of 120 or 180 mg once daily, adverse events were similar in
fexofenadine hydrochloride- and placebo-treated subjects. Table 1 also lists
adverse experiences that were reported by greater than 2% of subjects treated
with fexofenadine hydrochloride tablets at doses of 180 mg once daily and that
were more common with fexofenadine hydrochloride than placebo.

The incidence of adverse events, including drowsiness, was not dose-related
and was similar across subgroups defined by age, gender, and race.

The frequency and magnitude of laboratory abnormalities were similar in
fexofenadine hydrochloride- and placebo-treated subjects.

Table 2 lists adverse experiences in subjects aged 6 to 11 years
of age which were reported by greater than 2% of subjects treated with
fexofenadine hydrochloride tablets at a dose of 30 mg twice daily in
placebo-controlled seasonal allergic rhinitis studies in the United States and
Canada that were more common with fexofenadine hydrochloride than placebo.

The safety of fexofenadine hydrochloride in the treatment of chronic
idiopathic urticaria in pediatric patients 6 to 11 years of age is based on the
safety profile of fexofenadine hydrochloride in adults and adolescent patients
at doses equal to or higher than the recommended dose (see Pediatric Use).

Events that have been reported during controlled clinical trials involving
seasonal allergic rhinitis and chronic idiopathic urticaria subjects with
incidences less than 1% and similar to placebo and have been rarely reported
during postmarketing surveillance include: insomnia, nervousness, and sleep
disorders or paroniria. In rare cases, rash, urticaria, pruritus and
hypersensitivity reactions with manifestations such as angioedema, chest
tightness, dyspnea, flushing and systemic anaphylaxis have been reported.

Table 1 Adverse experiences in subjects aged 12 years and older
reported in placebo-controlled seasonal allergic rhinitis clinical trials in the
United States

Once daily dosing with fexofenadine
hydrochloride tabletsat rates of greater than 2%

Adverse experience

Fexofenadine 180 mgOnce
Daily(n=283)

Placebo(n=293)

Headache

10.6%

7.5%

Upper Respiratory Tract Infection

3.2%

3.1%

Back Pain

2.8%

1.4%

Table 2 Adverse experiences reported in placebo-controlled seasonal
allergic rhinitis studies in pediatric subjects aged 6 to 11 in the United
States and Canada at rates of greater than 2%

Adverse experience

Fexofenadine 30 mgTwice
Daily(n=209)

Placebo(n=229)

Headache

7.2%

6.6%

Accidental Injury

2.9%

1.3%

Coughing

3.8%

1.3%

Fever

2.4%

0.9%

Pain

2.4%

0.4%

Otitis Media

2.4%

0.0%

Upper Respiratory Tract Infection

4.3%

1.7%

Table 3 Adverse experiences reported in subjects 12 years of age and
older in placebo-controlled chronic idiopathic urticaria studies

Twice-daily dosing with fexofenadine
hydrochloride in studiesin the United States and Canada at rates of greater
than 2%

Adverse experience

Fexofenadine 60 mgTwice Daily(n=191)

Placebo(n=183)

Dyspepsia

4.7%

4.4%

Myalgia

2.6%

2.2%

Back Pain

2.1%

1.1%

Dizziness

2.1%

1.1%

Pain in extremity

2.1%

0.0%

Once-daily dosing with fexofenadine
hydrochloride in a studyin the United States at rates of greater than
2%

Adverse experience

Fexofenadine 180 mgOnce
Daily(n=167)

Placebo(n=92)

Headache

4.8%

3.3%

Nasopharyngitis

2.4%

2.2%

Upper respiratory tract infection

2.4%

2.2%

Reports of fexofenadine hydrochloride overdose have been
infrequent and contain limited information. However, dizziness, drowsiness, and
dry mouth have been reported. Single doses of fexofenadine hydrochloride up to
800 mg (6 healthy volunteers at this dose level), and doses up to 690 mg twice
daily for 1 month (3 healthy volunteers at this dose level) or 240 mg once daily
for 1 year (234 healthy volunteers at this dose level) were administered without
the development of clinically significant adverse events as compared to
placebo.

In the event of overdose, consider standard measures to remove any unabsorbed
drug. Symptomatic and supportive treatment is recommended. Following
administration of terfenadine, hemodialysis did not effectively remove
fexofenadine, the major active metabolite of terfenadine, from blood (up to 1.7%
removed).

No deaths occurred at oral doses of fexofenadine hydrochloride up to 5000
mg/kg in mice (110 times the maximum recommended human daily oral dose in adults
and 200 times the maximum recommended human daily oral dose in children based on
mg/m) and up to 5000 mg/kg in rats (230 times the
maximum recommended human daily oral dose in adults and 400 times the maximum
recommended human daily oral dose in children based on mg/m). Additionally, no clinical signs of toxicity or gross
pathological findings were observed. In dogs, no evidence of toxicity was
observed at oral doses up to 2000 mg/kg (300 times the maximum recommended human
daily oral dose in adults and 530 times the maximum recommended human daily oral
dose in children based on mg/m).

The recommended dose of Fexofenadine Hydrochloride Tablets is 60
mg twice daily, or 180 mg once daily with water. A dose of 60 mg once daily is
recommended as the starting dose in patients with decreased renal function (see
CLINICAL PHARMACOLOGY).

The recommended dose of Fexofenadine Hydrochloride Tablets is 30
mg twice daily with water. A dose of 30 mg once daily is recommended as the
starting dose in pediatric patients with decreased renal function (see CLINICAL PHARMACOLOGY).

The recommended dose of Fexofenadine Hydrochloride Tablets is 60
mg twice daily or 180 mg once daily with water. A dose of 60 mg once daily is
recommended as the starting dose in patients with decreased renal function (see
CLINICAL PHARMACOLOGY).

The recommended dose of Fexofenadine Hydrochloride Tablets is 30
mg twice daily with water. A dose of 30 mg once daily is recommended as the
starting dose in pediatric patients with decreased renal function (see CLINICAL PHARMACOLOGY).

Fexofenadine Hydrochloride Tablets are coated with a peach colored film
coating. Tablets have the following unique identifiers: 30 mg tablets have 03 on
one side, 60 mg tablets have 06 on one side, and 180 mg tablets have 018 on one
side.

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